Abstract Testosterone is often used to improve the physiological function. But increased testosterone levels affect blood lipids and cause inflammation and oxidative stress, which are risk factors for vascular diseases. This study aimed at investigating the effects of testosterone on cerebral vascular injury using an established intracranial aneurysm (IA) model. Sixteen-week-old female C57Bl/6 mice were subcutaneously infused with testosterone propionate (TP; 5 mg/kg day) or plain soybean oil (controls) for 6 weeks. After 2 weeks of treatment, mice were given angiotensin II-elastase for another 4 weeks. The results showed that TP significantly increased cell apoptosis and reactive oxygen species production in cerebral artery, together with increases in plasma tumor necrosis factor-α (TNF-α) levels and in urinary 8-isoprostane levels. Plasma assays showed that 2 weeks after TP or soybean oil administration, the high-density lipoprotein (HDL) level was higher in the TP group than in controls. In vitro studies showed that testosterone increased TNF-α and monocyte chemotactic protein-1 mRNA and protein expression levels in RAW 264.7 macrophages. In summary, by reducing the HDL level, TP aggravates cerebral artery injury by increasing cell apoptosis, inflammation, and oxidative stress.

中文翻译：

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睾酮通过降低血浆高密度脂蛋白水平加重脑血管损伤

摘要 睾酮常用于改善生理机能。但睾酮水平升高会影响血脂并引起炎症和氧化应激，这些都是血管疾病的危险因素。本研究旨在使用已建立的颅内动脉瘤 (IA) 模型研究睾酮对脑血管损伤的影响。16 周大的雌性 C57Bl/6 小鼠皮下注射丙酸睾酮（TP；每天 5 毫克/公斤）或纯大豆油（对照）6 周。治疗 2 周后，再给小鼠注射血管紧张素 II-弹性蛋白酶 4 周。结果表明，TP 显着增加脑动脉细胞凋亡和活性氧的产生，同时增加血浆肿瘤坏死因子-α（TNF-α）水平和尿 8-异前列烷水平。血浆检测显示，TP 或豆油给药 2 周后，TP 组的高密度脂蛋白 (HDL) 水平高于对照组。体外研究表明，睾酮增加了 RAW 264.7 巨噬细胞中 TNF-α 和单核细胞趋化蛋白-1 mRNA 和蛋白质的表达水平。总之，通过降低HDL水平，TP通过增加细胞凋亡、炎症和氧化应激来加重脑动脉损伤。